Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy

• Published in: Pathogens (Basel) Vol. 10; no. 11; p. 1488
• Main Authors: Farcomeni, Stefania, Moretti, Sonia, Fimiani, Caterina, Sulekova, Lucia Fontanelli, Vescio, Fenicia, Sernicola, Leonardo, Maggiorella, Maria T., Remoli, Anna Lisa, Picconi, Orietta, Mosca, Luciana, Esvan, Rozenn, Biliotti, Elisa, Ciccozzi, Massimo, Sgarbanti, Marco, Taliani, Gloria, Borsetti, Alessandra
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 15.11.2021; MDPI
• Subjects: Antiretroviral agents; Antiretroviral therapy; Antiviral agents; Biomarkers; CD4 antigen; CD8 antigen; Cell activation; Cell differentiation; Chemokines; DAA direct-acting antivirals; Dioxygenase; Drug therapy; Gene expression; HCV infection; HCV/HIV coinfection; Hepatitis C; HIV; Human immunodeficiency virus; immune activation; Immune response; Immune system; Immunological memory; Immunology; indoleamine 2-3 dioxygenase (IDO) activity; Infections; Inflammation; Interferon; Interferon regulatory factor; interferon-stimulated gene (ISG) expression; IP-10 protein; Liver; Liver diseases; Lymphocytes T; Patients; Peripheral blood mononuclear cells; Phenotypes; Plasma; Stiffness; Therapy; Viruses; United States > US
• ISSN: 2076-0817; 2076-0817
• DOI: 10.3390/pathogens10111488

Background: Direct-acting antivirals (DAAs) treatment, although highly efficacious for the treatment of hepatitis C virus (HCV) infection, may not completely reconstitute the HCV-mediated dysregulated immune system, especially in patients co-infected with human immunodeficiency virus (HIV) and HCV. Objectives: We aimed to evaluate the impact of HCV eradication following DAA therapy on the immune system and liver disease improvement through comparative monitoring of 10 HCV mono-infected and 10 HCV/HIV co-infected patients under combined antiretroviral therapy (cART). Early and late longitudinal phenotypic changes in peripheral blood mononuclear cell (PBMC) subsets, T-cell activation, differentiation and exhaustion, as well as inflammatory biomarkers, indoleamine 2-3 dioxygenase (IDO) activity, and liver stiffness, APRI and FIB-4 scores were assessed. Materials and Methods: Samples were obtained at baseline (T0), week 1 (T1), week 2 (T2), week 12 (T3, end of treatment, EOT), and month 9 (T4, end of follow-up, 36 weeks post EOT). Results: All patients achieved a sustained virological response (SVR 12) after DAA treatment. Overall, changes of the T-cell immune phenotypes were greater in HCV/HIV co-infected than in HCV mono-infected, due to an increase in CD4+ and CD8+ T-cell percentages and of CD8+ T-cell activation and memory markers, in particular at the end of follow-up. On the other end, HCV mono-infected showed changes in the activation profile and in the memory CD4+ T-cell compartment. In HCV/HIV co-infected, a decrease in the IDO activity by DAA treatment was observed; conversely, in HCV mono-infected, it resulted unmodified. Regarding inflammatory mediators, viral suppression was associated with a reduction in IP-10 levels, while interferon regulatory factor (IRF)-7, interferon (IFN)-β, and interferon (IFN)-γ levels were downregulated during therapy and increased post therapy. A decrease in liver stiffness, APRI, and FIB-4 scores was also observed. Conclusions: Our study suggests that, although patients achieved HCV eradication, the immune activation state in both HCV mono-infected and HCV/HIV co-infected patients remains elevated for a long time after the end of DAA therapy, despite an improvement of liver-specific outcomes, meanwhile highlighting the distinct immunophenotypic and inflammatory biomarker profile between the groups of patients.